A study of post-menopausal women who took the drug gabapentin to control hot flashes shows that it appears to be a safe and effective alternative to hormone replacement therapy. The research, conducted by the University of Rochester Medical Center, is reported in the February 2003 issue of Obstetrics and Gynecology. This is a significant development for an estimated 40 million American women who are at least 51 years old, the average age at which natural menopause begins. Millions of them are looking for new ways to calm symptoms, after two rigorous studies last year associated hormone replacement therapy (HRT) with an increased risk of heart disease and breast cancer.
Thomas J. Guttuso Jr., M.D., a neurologist at the University's Strong Memorial Hospital, first observed the unlikely connection between the seizure/migraine medication and hot flashes back in 1999. A female patient who was prescribed gabapentin for headaches told Guttuso that it did a better job at taming her hot flashes. This information led Guttuso to investigate further.
His study is the first, randomized, placebo-controlled clinical trial to confirm the observation that gabapentin relieves hot flashes. The National Institutes of Health and the University of Rochester Institutional Research Fund paid for the study. In addition, the University has obtained a patent for the use of gabapentin as a treatment for hot flashes. (The FDA has approved gabapentin for treatment of epileptic seizures and shingles pain.)
"It is very exciting to have an effective, non-hormonal hot flash treatment for women who have chosen to discontinue their hormone replacement therapy," Guttuso says.
Menopause is a natural process in which the body loses estrogen. But many women cannot tolerate therapy that replaces the lost hormones, due to a history of liver or gallbladder disease or other medical conditions. Furthermore, many women are no longer interested in hormone therapy due to the associated increased rates of breast cancer and heart disease. And several non-hormone therapies - black cohosh, soy, vitamin E., clonidine, etc., - show inconsistent findings in clinical trials, or are not very effective.
Guttuso's study involved 59 women who had more than seven hot flashes a day. During the 12-week research period, the women kept diaries, recording hot flash frequency and severity. Patients were randomly assigned to either gabapentin or an identically appearing placebo capsule.
The results: the women taking a low dose of gabapentin (900 mg/day) reported a 54-percent reduction in hot flash activity, compared to a 31-percent reduction in the placebo group. Hot flash activity combines both hot flash frequency and severity into one score. After the study was complete, Guttuso extended an open-label treatment phase to those women who wanted to enroll. During that additional five-week period, higher doses of gabapentin (up to 2,700 mg/day) were associated with an even larger reduction - up to 67 percent - in hot flash activity.
Gabapentin side effects include sleepiness, dizziness and leg edema. Approximately 13 percent of the study participants dropped out due to side effects, Guttuso reports. "Patients should slowly increase gabapentin dosing over one to two weeks to minimize side effects," he says. "Taking gabapentin with food also helps to minimize these side effects."
It is not known exactly why gabapentin relieves hot flashes. Guttuso theorizes that the drug works on calcium channels in the brain's temperature regulatory center, known as the hypothalamus. Gabapentin's interaction with these calcium channels may lead to a decrease in the release of brain neurotransmitter chemicals called tachykinins. However, more studies are needed to clarify gabapentin's mechanism of action.
